Backround and Objectives The preferred antibiotic treatment of chronic Lyme disease, and that of chronic neuroborreliosis in particular, is still not fully defined. In an effort to develop improved and more reliable remedies for chronic Lyme disease, an eclectic treatment regimen has been designed. It includes two antibiotics that are highly effective against both acute and chronic Lyme disease ceftriaxone (2 g, IV, once a day, 30 days) and doxycycline (100 mg/kg, bid, per os, 60 days). The goal of this project is to assess the efficacy of this combination regimen, originally devised for humans, in rhesus macaques. More specifically, to monitor the elimination of a Borrelia burgdorferi (Bb) infection from all organs commonly targeted by this spirochete, and especially from the central nervous system. Results A strain of Bb(NT1) which was isolated from the cerebrospinal fluid of a Lyme disease patient and was shown to be neurotropic in needle-inoculated monkeys, will be employed. In an initial experiment involving 7 animals (6 experimental and one control), the neurotropism of NT1 will be verified after infecting the monkeys with ticks carrying NT1. This experiment is now underway. The nymphal ticks employed (both infected and uninfected) were generated in the tick facility of the Tulane Primate Center. Future Directions Similar ticks will be employed then to infect 24 animals for the efficacy trial. The faithfulness with which the model reproduces both human Lyme disease and the pharmacokinetic properties of ceftriaxone and doxycycline seen in humans, may permit to extrapolate the efficacy results to the human situation. The accessibility to multiple serially-collected biopsies and fluid samples, as well as the possibility to survey all organs postmortem for signs of the spirochete itself and of the pathology it induces, will insure the success of this efficacy trial.